Targeting MAO-B with Small-Molecule Inhibitors: A Decade of Advances in Anticancer Research (2012–2024)
Monoamine oxidase B (MAO-B) is a key enzyme in the mitochondrial outer membrane, pivotal for the oxidative deamination of biogenic amines. Its overexpression has been implicated in the pathogenesis of several cancers, including glioblastoma and colorectal, lung, renal, and bladder cancers, primarily...
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2024-12-01
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| author | Iyman Alsaad Diana M. A. Abdel Rahman Ola Al-Tamimi Shayma’a A. Alhaj Dima A. Sabbah Rima Hajjo Sanaa K. Bardaweel |
| author_facet | Iyman Alsaad Diana M. A. Abdel Rahman Ola Al-Tamimi Shayma’a A. Alhaj Dima A. Sabbah Rima Hajjo Sanaa K. Bardaweel |
| author_sort | Iyman Alsaad |
| collection | DOAJ |
| description | Monoamine oxidase B (MAO-B) is a key enzyme in the mitochondrial outer membrane, pivotal for the oxidative deamination of biogenic amines. Its overexpression has been implicated in the pathogenesis of several cancers, including glioblastoma and colorectal, lung, renal, and bladder cancers, primarily through the increased production of reactive oxygen species (ROS). Inhibition of MAO-B impedes cell proliferation, making it a potential therapeutic target. Various monoamine oxidase B inhibitors have shown promise in inhibiting tumor growth and inducing apoptosis across different cancer types. In this review, we investigate MAO-B network biology, which highlighted glycolysis pathways as notable links between MAO-B and cancer. Further molecular modeling analysis illustrated the basis of MAO-B ligand binding, revealing a hydrophobic binding pocket, with key residues such as Tyr398 and Tyr435 playing crucial roles in substrate oxidation. MAO-B inhibitors that were reportsed in the literature (2012–2024) and their potential application in cancer therapy were discussed, highlighting key molecular scaffolds, such as propargyl analogs of phenyl alkyl amines, hydrazine derivatives, cyclopropylamine derivatives, MAO-B activated pro-drugs, and natural phenylpropanoid derivatives. The reported literature underscores the therapeutic potential of MAO-B inhibitors as versatile anticancer agents, warranting further investigation to optimize their efficacy and specificity across various malignancies. |
| format | Article |
| id | doaj-art-214c4d4385cb4bbe9de47c33c69d6ec8 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-12-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj-art-214c4d4385cb4bbe9de47c33c69d6ec82025-01-10T13:18:57ZengMDPI AGMolecules1420-30492024-12-0130112610.3390/molecules30010126Targeting MAO-B with Small-Molecule Inhibitors: A Decade of Advances in Anticancer Research (2012–2024)Iyman Alsaad0Diana M. A. Abdel Rahman1Ola Al-Tamimi2Shayma’a A. Alhaj3Dima A. Sabbah4Rima Hajjo5Sanaa K. Bardaweel6Department of Pharmaceutical Sciences, School of Pharmacy, University of Jordan, Amman 11942, JordanDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Jordan, Amman 11942, JordanDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Jordan, Amman 11942, JordanDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Jordan, Amman 11942, JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, JordanDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Jordan, Amman 11942, JordanMonoamine oxidase B (MAO-B) is a key enzyme in the mitochondrial outer membrane, pivotal for the oxidative deamination of biogenic amines. Its overexpression has been implicated in the pathogenesis of several cancers, including glioblastoma and colorectal, lung, renal, and bladder cancers, primarily through the increased production of reactive oxygen species (ROS). Inhibition of MAO-B impedes cell proliferation, making it a potential therapeutic target. Various monoamine oxidase B inhibitors have shown promise in inhibiting tumor growth and inducing apoptosis across different cancer types. In this review, we investigate MAO-B network biology, which highlighted glycolysis pathways as notable links between MAO-B and cancer. Further molecular modeling analysis illustrated the basis of MAO-B ligand binding, revealing a hydrophobic binding pocket, with key residues such as Tyr398 and Tyr435 playing crucial roles in substrate oxidation. MAO-B inhibitors that were reportsed in the literature (2012–2024) and their potential application in cancer therapy were discussed, highlighting key molecular scaffolds, such as propargyl analogs of phenyl alkyl amines, hydrazine derivatives, cyclopropylamine derivatives, MAO-B activated pro-drugs, and natural phenylpropanoid derivatives. The reported literature underscores the therapeutic potential of MAO-B inhibitors as versatile anticancer agents, warranting further investigation to optimize their efficacy and specificity across various malignancies.https://www.mdpi.com/1420-3049/30/1/126cancermonoamine oxidase B (MAO-B)MAO-B inhibitorsMAO-B network biologyMAO-B ligand interactionsanticancer agents |
| spellingShingle | Iyman Alsaad Diana M. A. Abdel Rahman Ola Al-Tamimi Shayma’a A. Alhaj Dima A. Sabbah Rima Hajjo Sanaa K. Bardaweel Targeting MAO-B with Small-Molecule Inhibitors: A Decade of Advances in Anticancer Research (2012–2024) Molecules cancer monoamine oxidase B (MAO-B) MAO-B inhibitors MAO-B network biology MAO-B ligand interactions anticancer agents |
| title | Targeting MAO-B with Small-Molecule Inhibitors: A Decade of Advances in Anticancer Research (2012–2024) |
| title_full | Targeting MAO-B with Small-Molecule Inhibitors: A Decade of Advances in Anticancer Research (2012–2024) |
| title_fullStr | Targeting MAO-B with Small-Molecule Inhibitors: A Decade of Advances in Anticancer Research (2012–2024) |
| title_full_unstemmed | Targeting MAO-B with Small-Molecule Inhibitors: A Decade of Advances in Anticancer Research (2012–2024) |
| title_short | Targeting MAO-B with Small-Molecule Inhibitors: A Decade of Advances in Anticancer Research (2012–2024) |
| title_sort | targeting mao b with small molecule inhibitors a decade of advances in anticancer research 2012 2024 |
| topic | cancer monoamine oxidase B (MAO-B) MAO-B inhibitors MAO-B network biology MAO-B ligand interactions anticancer agents |
| url | https://www.mdpi.com/1420-3049/30/1/126 |
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